D Dimer test in VTE

Marwan Adwan
 Objectives
Epidemiology of VTE
Imaging modalities in VTE
D Dimer
Causes of ↑ D Dimer
Different tests
EBM data
 Epidemiology of PE
Incidence (USA) 23/100,000/year
1 year mortality 19%
10% will have recurrent event
Mortality in recurrent PE is 45%
Therapy with LMWH & thrombolysis has not altered
mortality & morbidity
attributed to the fact that most PEs remain unsuspected
and unrecognised before death
necropsy studies indicate that PE is overlooked as the
primary or contributory cause of death in up to 84% of
cases

B H Mavromatis et.al. J Clin Pathol 2001;54:664–668

 Epidemiology of DVT
Incidence (USA) 100,000-300,000/yr
Of patients presenting with symptoms of DVT,
only 30% actually have DVT
20% of patients who present with symptomatic
DVT of the leg have isolated calf-vein
thrombosis
30% of those patients will have subsequent
extension of the clot into the proximal system

Paula Bockenstedt. d-Dimer in Venous Thromboembolism NEJM 349;13

Imaging modalities of VTE
Invasive:
– Problem: Small risk of complications
Non-invasive:
– Problem: limited sensitivity

We need a diagnostic tool that is non-invasive &

sensitive
 D Dimer
Sensitive
But not specific
Good in excluding rather than confirming
diagnosis
WHAT IS D DIMER?
 D Dimer
A protein that is released into the
circulation during the process of fibrin clot
breakdown.
Represents an area of cross-linked fibrin
degradation product that originated from
the breaking down of the fibrin clot
network during the body’s repair
mechanisms.
 D Dimer
D-dimer in circulation is an indicator of a
blood clot being formed and broken down
somewhere in the body.
Not pathognomonic of VTE
Causes of raised D Dimer
 Thrombosis:
DVT / PE
DIC
MI
Valvular (AF)
Stroke
Vasculitis
Sickle cell crisis
 Non-clot causes:

Carcinomas
hepatic and renal insufficiency
Surgery
Septicaemia / infection
major trauma
Pregnancy
Hemorrhage
Elderly: ↑ linearly with age
 D. Dimer tests
Very sensitive, but non-specific for the
diagnosis of deep vein thrombosis and PE

high values are not as helpful in

establishing the diagnosis of DVT/PE as
normal values are in excluding the
diagnosis
assays rely on monoclonal antibodies.
The first MoAb was D Dimer-3B6/22
introduced in 1990s
Others have been developed
Which test?
Different tests
Different sensitivities & specificities
– ELISA
– Latex
– SimpliRED
– Immunofiltration assay
– Immunoturbidimetric assay
 ELISA
High sensitivity 90-100%
low specificity 40%
Normal value has high NPP, but occurs in
a small no. of patients
quantitative
time consuming
Use limited
 SimliRED
RBC agglutination assay
Result in < 5 min
Intermediate sensitivity 85%
Intermediate specificity 70%
NPP lower, but occurs in higher no. of
patients
 Latex agglutination test
Lower sensitivity
lower NPV when compared with the ELISA
method
Quick & Cheap
Immunoturbidimetric technique
2nd generation latex agglutination
High sensitivity
Intermediate specificity
D-dimer has a half life of approximately 6 hours
in the circulation of individuals with normal renal
function
Patients with stabilised clots and not undergoing
active fibrin deposition and plasmin activation,
may not give detectable D-dimer elevations
The larger the clot size, the higher the expected
level of circulating D-dimer. The converse is also
true
Clinical probability
Kelly et. al. Arch intern med 2002;162:747-756
Can we omit further investigation
if D dimer is normal?
 Pierre et.al.

918 patients suspected DVT/PE

159 had normal D dimer
Not investigated further
None developed VTE after 3/12
Taking clinical probability into
account
 Kearon et.al.

445 patients suspected DVT

40% (177) had low clinical probability &
negative D dimer
Only 1 out of 177 developed VTE after
3/12
NPV = 176 = 99.4%
177
What about PE?
 Wells et.al.
930 patients suspected PE
Those with low clinical suspicion & -ve D dimer
were not investigated further
All others had V/Q
If V/Q non-diagnostic  doppler both legs
47% (437) had low clinical probability & D dimer
Only 1 developed VTE in 3/12
NPV = 436 = 99.5%
437
Take home message
DVT can be ruled out in a patient with low
clinical probability & negative D Dimer